Molecularly cloned proviruses of the Snyder-Theilen (ST), Gardner-Arnstein (GA) and McDonough (SM) strains of feline sarcoma virus (FeSV) were used to characterize two viral oncogenes (v-fes and v-fms) responsible for FeSV-induced transformation and tumorigenesis. The complete nucleotide sequences of the ST- and GA-FeSV v-fes genes, each of which encodes a tyrosine-specific protein kinase, have been determined. The predicted amino acid sequences of these proteins show that they are homologous to proteins encoded by other oncogenes (v-fps, v-src, and v-yes) which also exhibit tyrosine kinase activity. DNA transfection experiments using plasmids containing molecularly subcloned portions of GA-FeSV formally showed that v-fes sequences were necessary for transformation. Chimeric transforming viruses and mutants generated by recombinant DNA techniques were used to map viral functions which regulate expression of the transforming gene. The v-fms oncogene was shown to differ from v-fes and was demonstrated to encode a transforming glycoprotein. Monoclonal antibodies were prepared to the v-fms product and permitted assays of its steady state levels in transformed cells. Portions of the human c-fms proto-oncogene were molecularly cloned and partially characterized.